Disposition of intravenous propylthiouracil

Propylthiouracil was administered to 10 healty, male volunteers by a short intravenous infusion. Plasma and urinary drug concentrations were determined by a specific high-performance liquid chromatography assay, and protein binding was determined by equilibrium dialysis. After infusion, the plasma concentrations declined biexponentially, and the following median parameters (and ranges) were determined: clearance 273.5 ml/min (159.5-377.8 ml/min); free drug clearance, 1537.7 ml/min (985.9-1927.3 ml/min); apparent volume of distribution, 28.0 liters (22.7-44.4 liters); apparent elimination half-life, 1.28 hr (0.88-2.05 hr); k21, 3.12 hr-1 (1.06-5.36 hr-1): alpha 7.34 hr-1 (1.94-25.03 hr-1): Vc 9.40 liters (5.16-18.58 liters). In urine, only 1.28 per cent (0.03-2.01 per cent) of the administered dose was recovered over 24 hours as unchanged drug. The ratio (1.2 per cent) of urinary clearance (3.2 ml/min) to plasma clearance is far less (P less than 0.001) than the free fraction in plasma (median 18.2 percent, range 16.2-20.2 per cent) and this suggests that there is significant renal tubular reabsorption of propylthiouracil. In healthy subjects, both intraindividual and interindividual variation of protein binding is modest, and free drug clearance can be predicted from total drug clearance (y =- 257.6 + 4.56x, r = 0.95, P less than 0.001).